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Q1LZ53

- DNM3A_RAT

UniProt

Q1LZ53 - DNM3A_RAT

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Protein

DNA (cytosine-5)-methyltransferase 3A

Gene
Dnmt3a
Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at transcript leveli

Functioni

Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNA methylation is coordinated with methylation of histones. It modifies DNA in a non-processive manner and also methylates non-CpG sites. May preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1. Plays a role in paternal and maternal imprinting. Required for methylation of most imprinted loci in germ cells. Acts as a transcriptional corepressor for ZBTB18. Can actively repress transcription through the recruitment of HDAC activity By similarity.

Catalytic activityi

S-adenosyl-L-methionine + DNA = S-adenosyl-L-homocysteine + DNA containing 5-methylcytosine.

Enzyme regulationi

Activated by binding to the regulatory factor DNMT3L By similarity.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei660 – 6601S-adenosyl-L-methionine By similarity
Active sitei706 – 7061 By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri489 – 51931GATA-type; atypicalAdd
BLAST
Zinc fingeri530 – 58657PHD-type; atypicalAdd
BLAST

GO - Molecular functioni

  1. chromatin binding Source: Ensembl
  2. DNA (cytosine-5-)-methyltransferase activity Source: UniProtKB
  3. DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates Source: RGD
  4. DNA binding Source: UniProtKB
  5. metal ion binding Source: UniProtKB-KW
  6. unmethylated CpG binding Source: RGD

GO - Biological processi

  1. C-5 methylation of cytosine Source: GOC
  2. cellular response to amino acid stimulus Source: Ensembl
  3. DNA methylation Source: UniProtKB
  4. DNA methylation involved in embryo development Source: Ensembl
  5. DNA methylation involved in gamete generation Source: Ensembl
  6. DNA methylation on cytosine within a CG sequence Source: RGD
  7. hypermethylation of CpG island Source: Ensembl
  8. methylation-dependent chromatin silencing Source: Ensembl
  9. negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
  10. regulation of gene expression by genetic imprinting Source: Ensembl
  11. S-adenosylhomocysteine metabolic process Source: RGD
  12. S-adenosylmethioninamine metabolic process Source: RGD
  13. spermatogenesis Source: Ensembl
  14. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Methyltransferase, Repressor, Transferase

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, S-adenosyl-L-methionine, Zinc

Enzyme and pathway databases

ReactomeiREACT_212012. PRC2 methylates histones and DNA.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA (cytosine-5)-methyltransferase 3A (EC:2.1.1.37)
Short name:
Dnmt3a
Gene namesi
Name:Dnmt3a
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 6

Organism-specific databases

RGDi1303336. Dnmt3a.

Subcellular locationi

Nucleus By similarity. Cytoplasm By similarity

GO - Cellular componenti

  1. chromosome, centromeric region Source: Ensembl
  2. cytoplasm Source: UniProtKB
  3. euchromatin Source: UniProtKB
  4. nuclear heterochromatin Source: Ensembl
  5. nuclear matrix Source: UniProtKB
  6. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 908908DNA (cytosine-5)-methyltransferase 3APRO_0000313030Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei102 – 1021Phosphoserine By similarity
Modified residuei239 – 2391Phosphoserine By similarity
Modified residuei251 – 2511Phosphoserine By similarity
Modified residuei257 – 2571Phosphothreonine By similarity

Post-translational modificationi

Sumoylated; sumoylation disrupts the ability to interact with histone deacetylases (HDAC1 and HDAC2) and repress transcription By similarity.

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ1LZ53.

PTM databases

PhosphoSiteiQ1LZ53.

Expressioni

Gene expression databases

GenevestigatoriQ1LZ53.

Interactioni

Subunit structurei

Heterotetramer composed of 1 DNMT3A homodimer and 2 DNMT3L subunits (DNMT3L-DNMT3A-DNMT3A-DNMT3L) By similarity. Interacts with DNMT1 and DNMT3B. Binds the ZBTB18 transcriptional repressor. Interacts with SETDB1. Associates with HDAC1 through its ADD domain By similarity. Interacts with the PRC2/EED-EZH2 complex By similarity. Interacts with UBC9, PIAS1 and PIAS2 By similarity. Interacts with MPHOSPH8. Interacts with histone H3 that is not methylated at 'Lys-4' (H3K4). Interacts with UHRF1 By similarity.

Structurei

3D structure databases

ProteinModelPortaliQ1LZ53.
SMRiQ1LZ53. Positions 279-420, 623-908.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini257 – 31559PWWPAdd
BLAST
Domaini478 – 610133ADDAdd
BLAST
Domaini630 – 908279SAM-dependent MTase C5-typeAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni195 – 399205Interaction with DNMT1 and DNMT3B By similarityAdd
BLAST
Regioni490 – 58293Interaction with the PRC2/EED-EZH2 complex By similarityAdd
BLAST
Regioni637 – 6415S-adenosyl-L-methionine binding By similarity
Regioni682 – 6843S-adenosyl-L-methionine binding By similarity
Regioni887 – 8893S-adenosyl-L-methionine binding By similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi479 – 52749Cys-richAdd
BLAST

Domaini

The PWWP domain is essential for targeting to pericentric heterochromatin.

Sequence similaritiesi

Contains 1 ADD domain.
Contains 1 PWWP domain.

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri489 – 51931GATA-type; atypicalAdd
BLAST
Zinc fingeri530 – 58657PHD-type; atypicalAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiNOG70699.
GeneTreeiENSGT00390000008341.
HOGENOMiHOG000230875.
HOVERGENiHBG051381.
InParanoidiQ1LZ53.
KOiK17398.
OMAiFVGGMCQ.
OrthoDBiEOG7MWGW6.
PhylomeDBiQ1LZ53.
TreeFamiTF329039.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
InterProiIPR025766. ADD.
IPR018117. C5_DNA_meth_AS.
IPR001525. C5_MeTfrase.
IPR025811. C5_MeTrfase_3.
IPR000313. PWWP_dom.
IPR029063. SAM-dependent_MTases-like.
[Graphical view]
PfamiPF00145. DNA_methylase. 1 hit.
PF00855. PWWP. 1 hit.
[Graphical view]
SMARTiSM00293. PWWP. 1 hit.
[Graphical view]
SUPFAMiSSF53335. SSF53335. 1 hit.
PROSITEiPS51533. ADD. 1 hit.
PS00094. C5_MTASE_1. 1 hit.
PS50812. PWWP. 1 hit.
PS51679. SAM_MT_C5. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative promoter usage. Align

Isoform 1 (identifier: Q1LZ53-1) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

MPSSGPGDTS ISSLEREDDR KEGEEQEENR GKEERQEPSA TARKVGRPGR    50
KRKHPPVESS DTPKDPAVTT KSQPTAQDSG PSDLLPNGDL EKRSEPQPEE 100
GSPAAGQKGG APAEGEGTET PPEASRAVEN GCCVTKEGRG ASAGEGKEQK 150
QTNIESMKME GSRGRLRGGL GWESSLRQRP MPRLTFQAGD PYYISKRKRD 200
EWLARWKREA EKKAKVIAVM NAVEESQASG ESQKVEEASP PAVQQPTDPA 250
SPTVATTPEP VGADAGDKNA TKAADDEPEY EDGRGFGIGE LVWGKLRGFS 300
WWPGRIVSWW MTGRSRAAEG TRWVMWFGDG KFSVVCVEKL MPLSSFCSAF 350
HQATYNKQPM YRKAIYEVLQ VASSRAGKLF PACHDSDESD TGKAVEVQNK 400
QMIEWALGGF QPSGPKGLEP PEEEKNPYKE VYTDMWVEPE AAAYAPPPPA 450
KKPRKSTTEK PKVKEIIDER TRERLVYEVR QKCRNIEDIC ISCGSLNVTL 500
EHPLFIGGMC QNCKNCFLEC AYQYDDDGYQ SYCTICCGGR EVLMCGNNNC 550
CRCFCVECVD LLVGPGAAQA AIKEDPWNCY MCGHKGTYGL LRRREDWPSR 600
LQMFFANNHD QEFDPPKVYP PVPAEKRKPI RVLSLFDGIA TGLLVLKDLG 650
IQVDRYIASE VCEDSITVGM VRHQGKIMYV GDVRSVTQKH IQEWGPFDLV 700
IGGSPCNDLS IVNPARKGLY EGTGRLFFEF YRLLHDARPK EGDDRPFFWL 750
FENVVAMGVS DKRDISRFLE SNPVMIDAKE VSAAHRARYF WGNLPGMNRP 800
LASTVNDKLE LQECLEHGRI AKFSKVRTIT TRSNSIKQGK DQHFPVFMNE 850
KEDILWCTEM ERVFGFPVHY TDVSNMSRLA RQRLLGRSWS VPVIRHLFAP 900
LKEYFACV 908
Length:908
Mass (Da):101,669
Last modified:May 30, 2006 - v1
Checksum:i6CCE9EB4E9CEB409
GO
Isoform 2 (identifier: Q1LZ53-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-219: Missing.

Show »
Length:689
Mass (Da):77,825
Checksum:i1C75674CFC1C97BE
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 219219Missing in isoform 2. VSP_029986Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
BN000395 mRNA. Translation: CAE52317.1.
BN000396 mRNA. Translation: CAE52318.1.
RefSeqiNP_001003957.1. NM_001003957.1. [Q1LZ53-2]
NP_001003958.1. NM_001003958.1. [Q1LZ53-1]
UniGeneiRn.92659.

Genome annotation databases

EnsembliENSRNOT00000047210; ENSRNOP00000046524; ENSRNOG00000026649. [Q1LZ53-1]
GeneIDi444984.
KEGGirno:444984.

Keywords - Coding sequence diversityi

Alternative promoter usage

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
BN000395 mRNA. Translation: CAE52317.1 .
BN000396 mRNA. Translation: CAE52318.1 .
RefSeqi NP_001003957.1. NM_001003957.1. [Q1LZ53-2 ]
NP_001003958.1. NM_001003958.1. [Q1LZ53-1 ]
UniGenei Rn.92659.

3D structure databases

ProteinModelPortali Q1LZ53.
SMRi Q1LZ53. Positions 279-420, 623-908.
ModBasei Search...
MobiDBi Search...

PTM databases

PhosphoSitei Q1LZ53.

Proteomic databases

PaxDbi Q1LZ53.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000047210 ; ENSRNOP00000046524 ; ENSRNOG00000026649 . [Q1LZ53-1 ]
GeneIDi 444984.
KEGGi rno:444984.

Organism-specific databases

CTDi 1788.
RGDi 1303336. Dnmt3a.

Phylogenomic databases

eggNOGi NOG70699.
GeneTreei ENSGT00390000008341.
HOGENOMi HOG000230875.
HOVERGENi HBG051381.
InParanoidi Q1LZ53.
KOi K17398.
OMAi FVGGMCQ.
OrthoDBi EOG7MWGW6.
PhylomeDBi Q1LZ53.
TreeFami TF329039.

Enzyme and pathway databases

Reactomei REACT_212012. PRC2 methylates histones and DNA.

Miscellaneous databases

NextBioi 697058.

Gene expression databases

Genevestigatori Q1LZ53.

Family and domain databases

Gene3Di 3.40.50.150. 1 hit.
InterProi IPR025766. ADD.
IPR018117. C5_DNA_meth_AS.
IPR001525. C5_MeTfrase.
IPR025811. C5_MeTrfase_3.
IPR000313. PWWP_dom.
IPR029063. SAM-dependent_MTases-like.
[Graphical view ]
Pfami PF00145. DNA_methylase. 1 hit.
PF00855. PWWP. 1 hit.
[Graphical view ]
SMARTi SM00293. PWWP. 1 hit.
[Graphical view ]
SUPFAMi SSF53335. SSF53335. 1 hit.
PROSITEi PS51533. ADD. 1 hit.
PS00094. C5_MTASE_1. 1 hit.
PS50812. PWWP. 1 hit.
PS51679. SAM_MT_C5. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. "Identification of 11 pseudogenes in the DNA methyltransferase gene family in rodents and humans and implications for the functional loci."
    Lees-Murdock D.J., McLoughlin G.A., McDaid J.R., Quinn L.M., O'Doherty A., Hiripi L., Hack C.J., Walsh C.P.
    Genomics 84:193-204(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).

Entry informationi

Entry nameiDNM3A_RAT
AccessioniPrimary (citable) accession number: Q1LZ53
Secondary accession number(s): Q1LZ52
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: May 30, 2006
Last modified: September 3, 2014
This is version 70 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi